PROJECT SUMMARY ? PROJECT 2 Prescription drugs have transformed patient care over the last several decades with stunning benefits, but their use has also conferred risks; this is especially true for the elderly. We propose to study three commonly- prescribed but potentially risky groups of drugs (opioid analgesics, benzodiazepines, and non-benzodiazepine sedative hypnotics). We will explore how use of these drugs has changed over time and how their use, alone or in combination, is related to important health outcomes including falls, motor vehicle accidents, fractures and overdose events. Heightened susceptibility to the adverse effects of powerful drugs among near old, old, and very old adults makes study of these substances in aging populations essential to our understanding of their safety profile. But, these same drugs are important to high-quality, merciful management of pain, extreme anxiety and air hunger that can characterize end of life experience as well as many acute and chronic health conditions; underuse thus may be as burdensome as overuse. Our proposal has four aims: Aim 1: To describe patterns of risky drug receipt by the elderly, including opioid analgesics, benzodiazepines, sedative hypnotics. Aim 2: To measure outcomes related to risky drug receipt by the elderly. Aim 3: To explore clinician, health system, and external factors associated with potentially hazardous prescribing. Aim 4: To leverage natural experiments to identify plausible causes of hazardous prescribing patterns and plausibly causal effects of prescription drug use on adverse health events. Because we anticipate heterogeneous effects of these drugs in distinct populations, each aim will examine the overall population as well as sub-populations with feasible diverse vulnerabilities due to biologic factors; we will specifically study drug receipt, outcomes and predictors in groups defined by age, sex, race/ethnicity, poverty, long-term care residence and morbidities, including dementia and behavioral health conditions. This proposal addresses NIA priority research areas including ?aspects of marijuana and prescription opioid and benzodiazepine use in adults aged 50 and older,? ?health disparities and minority aging issues,? ?interactions of comorbid conditions, therapies for these conditions, and the efficacy of interventions to optimize the balance of benefits and risks for the older patient with multiple conditions,? and, in our planned subgroup analyses, ?social science research related to Alzheimer?s disease and related dementias.?